Method for producing thienopyrimidines

Abstract

The invention relates to a process for preparing compounds of the formula I In this process a 2-aminobenzothiophene-3-carboxylic ester of the formula II is reacted with a nitrile of the formula III N≡C—R 1   III in solution or suspension in a solvent in the presence of an acid.

What is claimed is:  
     
       1. A process for preparing a compound of formula I                    
       wherein R 1  is 
       a linear of branched alkyl radical having 1 to 10 carbon atoms, in which one or two CH 2  groups are optionally each replaced by a —CH═CH— group,  
       a cycloalkyl radical or cycloalkylalkylene radical having 5 to 12 carbon atoms, or  
       a phenyl radical or phenylmethyl radical  
       wherein the radicals are mono substituted with COOH, COOA, CONH 2 , CONHA, CON(A) 2  or CN, wherein A is an alkyl group having from 1 to 6 carbon atoms, 
       comprising reacting a 2-aminobenzothiophene-3-carboxylic ester of formula II                    
       wherein R 2  is a linear or branched alkyl group having 1 to 6 carbon atoms, with a nitrile of formula III 
       
         
           N≡C—R 1    III  
         
       
       wherein R 1  has the above meaning 
       in solution or suspension in a solvent in the presence of an acid,  
       wherein an excess of the acid is dissolved in the solvent, and subsequently the 2-aminobenzothiophene-3-carboxylic ester of formula II and the nitrile of the formula III are added. 
     
     
       2. A process for preparing a compound of formula I                    
       wherein R 1  is 
       a linear of branched alkyl radical having 1 to 10 carbon atoms, in which one or two CH 2  groups are optionally each replaced by a —CH═CH— group,  
       a cycloalkyl radical or cycloalkylalkylene radical having 5 to 12 carbon atoms, or  
       a phenyl radical or phenylmethyl radical  
       wherein the radicals are mono substituted with COOH, COOA, CONH 2 , CONHA, CON(A) 2  or CN, wherein A is an alkyl group having from 1 to 6 carbon atoms, 
       comprising reacting a 2-aminobenzothiophene-3-carboxylic ester of formula II                    
       wherein R 2  is a linear or branched alkyl group having 1 to 6 carbon atoms, 
       with a nitrile of formula III  
       
         
           N≡C—R 1    III  
         
       
       wherein R 1  has the above meaning 
       in solution or suspension in a solvent in the presence of an acid,  
       wherein the solvent is selected from the group consisting of ethers, alcohols, esters, water, amides, carboxylic acids, chlorinated hydrocarbons and mixtures thereof. 
     
     
       3. A process for preparing a compound of formula I                    
       wherein R 1  is 
       a linear of branched alkyl radical having 1 to 10 carbon atoms, in which one or two CH 2  groups are optionally each replaced by a —CH═CH— group,  
       a cycloalkyl radical or cycloalkylalkylene radical having 5 to 12 carbon atoms, or  
       a phenyl radical or phenylmethyl radical  
       wherein the radicals are mono substituted with COOH, COOA, CONH 2 , CONHA, CON(A) 2  or CN, wherein A is an alkyl group having from 1 to 6 carbon atoms, 
       comprising reacting a 2-aminobenzothiophene-3-carboxylic ester of formula II                    
       wherein R 2  is a linear or branched alkyl group having 1 to 6 carbon atoms, 
       with a nitrile of formula III  
       
         
           N≡C—R 1    III  
         
       
       wherein R 1  has the above meaning 
       in solution or suspension in a solvent in the presence of an acid,  
       wherein the acid is a Brönsted acid or a Lewis acid. 
     
     
       4. A process for preparing a compound of formula I                    
       wherein R 1  is 
       a linear of branched alkyl radical having 1 to 10 carbon atoms, in which one or two CH 2  groups are optionally each replaced by a —CH═CH— group,  
       a cycloalkyl radical or cycloalkylalkylene radical having 5 to 12 carbon atoms, or  
       a phenyl radical or phenylmethyl radical  
       wherein the radicals are mono substituted with COOH, COOA, CONH 2 , CONHA, CON(A) 2  or CN, wherein A is an alkyl group having from 1 to 6 carbon atoms, 
       comprising reacting a 2-aminobenzothiophene-3-carboxylic ester of formula II                    
       wherein R 2  is a linear or branched alkyl group having 1 to 6 carbon atoms, 
       with a nitrile of formula III  
       
         
           N≡C—R 1    III  
         
       
       wherein R 1  has the above meaning 
       in solution or suspension in a solvent in the presence of an acid,  
       wherein the reaction is carried out at a temperature of 10° C. to 100° C. 
     
     
       5. A process for preparing a compound of formula I                    
       wherein R 1  is 
       a linear of branched alkyl radical having 1 to 10 carbon atoms, in which one or two CH 2  groups are optionally each replaced by a —CH═CH— group,  
       a cycloalkyl radical or cycloalkylalkylene radical having 5 to 12 carbon atoms, or  
       a phenyl radical or phenylmethyl radical  
       wherein the radicals are mono substituted with COON, COOA, CONH 2 , CONHA, CON(A) 2  or CN, wherein A is an alkyl group having from 1 to 6 carbon atoms, 
       comprising reacting a 2-aminobenzothiophene-3-carboxylic ester of formula II                    
       wherein R 2  is a linear of branched alkyl group having 1 to 6 carbon atoms, 
       with a nitrile of formula III  
       
         
           N≡C—R 1    III  
         
       
       wherein R 1  has the above meaning 
       in solution or suspension in a solvent in the presence of an acid,  
       wherein addition of the acid is continued during the reaction to the solution or suspension. 
     
     
       6. A process for preparing a compound of formula IV                    
       wherein R 1  is 
       a linear of branched alkyl radical having 1 to 10 carbon atoms, in which one or two CH 2  groups are optionally each replaced by a —CH═CH— group,  
       a cycloalkyl radical or cycloalkylalkylene radical having 5 to 12 carbon atoms, or  
       a phenyl radical or phenylmethyl radical  
       wherein the radicals are mono substituted with COOH, COOA, CONH 2 , CONHA, CON(A) 2  or CN, wherein A is an alkyl group having from 1 to 6 carbon atoms, 
       comprising reacting a 2-aminobenzothiophene-3-carboxylic ester of formula II                    
       wherein R 2  is a linear or branched alkyl group having 1 to 6 carbon atoms, 
       with a nitrile of formula III  
       
         
           N≡C—R 1    III  
         
       
       wherein R 1  has the above meaning 
       in solution or suspension in a solvent in the presence of an acid, and  
       reacting the resultant product with SOCl 2 , POCl 3 , PCl 5 , or ClCOCOCl.  
     
     
       7. A process for preparing a compound of formula I according to  claim 1 , wherein R 2  is methyl. 
     
     
       8. A process or preparing a compound of formula I according to  claim 1 , wherein the solvent is sat rated with the acid. 
     
     
       9. A process or preparing a compound of formula I according to  claim 2 , wherein wherein the solvent is selected from the group consisting of ethers, alcohols, water, amides, carboxylic acids, chlorinated hydrocarbons and mixtures thereof. 
     
     
       10. A process for preparing a compound of formula I according to  claim 3 , wherein wherein the acid is hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, aluminium trichloride or boron trifluoride. 
     
     
       11. A process for preparing a compound of formula I according to  claim 4 , wherein the reaction is carried out at a temperature of 0° C. to 60° C. 
     
     
       12. A process for preparing a compound of formula I according to  claim 4 , wherein the reaction is carried out at a temperature of 10° C. to 50° C. 
     
     
       13. A process for preparing a compound of formula I according to  claim 1 , wherein R 1  is a cyclohexyl radical substituted COOA. 
     
     
       14. A process for preparing a compound of formula I according to  claim 2 , wherein R 1  is a cyclohexyl radical substituted COOA. 
     
     
       15. A process for preparing a compound of formula I according to  claim 3 , wherein R 1  is a cyclohexyl radical substituted COOA. 
     
     
       16. A process for preparing a compound of formula I according to  claim 4 , wherein R 1  is a cyclohexyl radical substituted COOA. 
     
     
       17. A process for preparing a compound of formula I according to  claim 5 , wherein R 1  is a cyclohexyl radical substituted COOA. 
     
     
       18. A process for preparing a compound of formula I according to  claim 6 , wherein R 1  is a cyclohexyl radical substituted COOA. 
     
     
       19. A process for preparing a compound of formula I, A process for preparing a compound of formula I                    
       wherein R 1  is 
       a linear of branched alkyl radical having 1 to 10 carbon atoms, in which one or two CH 2  groups are optionally each replaced by a —CH═CH— group,  
       a cycloalkyl radical or cycloalkylalkylene radical having 5 to 12 carbon atoms, or  
       a phenyl radical or phenylmethyl radical  
       wherein the radicals are mono substituted with COOH, COOA, CONH 2 , CONHA, CON(A) 2  or CN, wherein A is an alkyl group having from 1 to 6 carbon atoms, 
       comprising reacting a 2-aminobenzothiophene-3-carboxylic ester of formula II                    
       wherein R 2  is a linear or branched alkyl group having 1 to 6 carbon atoms, with a nitrile of formula III 
       
         
           N≡C—R 1    III  
         
       
       wherein R 1  has the above meaning 
       in solution or suspension in a solvent in the presence of an acid,  
       wherein the 2-aminobenzothiophene-3-carboxylic ester of formula II and the nitrile of the formula III are dissolved in the solvent and subsequently the acid is added. 
     
     
       20. A process for preparing a compound of formula I according to  claim 19 , wherein R 1  is a cyclohexyl radical substituted COOA. 
     
     
       21. A process for preparing a compound of formula I according to  claim 2 , wherein the solvent is dioxane.